Strategies for Monitoring Pathologic Conditions and Treatment Efficacy in Murine Models

Abstract

On the surface, the pathologies of infectious disease and cancer appear fundamentally different; however, there exist several commonalities including pharmacological targets and resistance mechanisms, immune response, and the role of commensal microbes for response to therapeutic intervention. The lessons learned from each of these pathologies can provide valuable insights which may benefit preclinical research as a whole. This dissertation represents the work of three distinct, but interrelated projects with the central focus on strategies for monitoring pathologic conditions and novel treatment efficacy of Staphylococcus aureus (S. aureus) infection and an improved method for monitoring longitudinal progression of cancer in preclinical models. Specifically, (1) the development of a device for semi-automated multi-angle in vivo bioluminescence, fluorescence, and X-ray imaging, (2) the efficacy of a novel probiotic, Bacillus amyloliquefaciens strain AP183, for the biocontrol of cutaneous S. aureus infection, and (3) investigation of species-specificity of S. aureus strains through bioinformatics and biochemical tests involving the prothrombin activator staphylocoagulase. In Chapter 2, we demonstrate the utility of our in-house developed system for multi-angle rotational optical imaging which we showed improved the accuracy and consistency of longitudinal bioluminescence imaging datasets in a model of prostate cancer. In Chapter 3, we evaluated the efficacy of a novel probiotic microorganism B. amyloliquefaciens strain AP183 for inhibiting S. aureus infection in vivo in a cutaneous wound model. And, in Chapter 4, we present new evidence that elucidates the mechanism of S. aureus clotting preference to specific host species.